We report the first example of a K+ channel β-subunit that is also a serine/threonine kinase. MPS-1 is a single–transmembrane domain protein that coassembles with voltage-gated K+ channel KVS-1 in the nervous system of the nematode Caenorhabditis elegans. Biochemical analysis shows that MPS-1 can phosphorylate KVS-1 and other substrates. Electrophysiological analysis in Chinese hamster ovary (CHO) cells demonstrates that MPS-1 activity leads to a significant decrease in the macroscopic current. Single-channel analysis and biotinylation assays indicate that MPS-1 reduces the macroscopic current by lowering the open probability of the channel. These data are consistent with a model that predicts that the MPS-1–dependent phosphorylation of KVS-1 sustains cell excitability by controlling K+ flux.
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We thank L. Runnels, A. Ryazanov and J. Lenard for their comments on the manuscript and Fulvio Sesti for help with the graphics. This work was supported by grant R01GM68581-01 from the US National Institutes of Health to F.S.
The authors declare no competing financial interests.
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Cai, S., Hernandez, L., Wang, Y. et al. MPS-1 is a K+ channel β-subunit and a serine/threonine kinase. Nat Neurosci 8, 1503–1509 (2005). https://doi.org/10.1038/nn1557
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